This invention relates to a method of alleviating pain. More particularly, this invention is directed to a method of alleviating pain, e.g., arthritic pain, lumbosacral pain, musculo-skeletal pain, pain associated with a sore throat, etc., by administering to a mammal in need of relief from pain tramadol and, to enhance the analgesic effectiveness of the tramadol, a nontoxic antagonist for the N-methyl-D-aspartate (NMDA) receptor such as dextromethorphan, dextrorphan or ketamine.
The compound cis-2-(dimethylamino)methyl!-1-(3-methoxyphenyl)cyclohexanol, commonly known as tramadol, is an analgesic commercially available as the hydrochloride salt. The process by which tramadol may be made is described in U.S. Pat. No. 3,652,589 the contents of which are incorporated herein by reference. Tramadol is chemically unrelated to the opiates, e.g., morphine, codeine, hydrocodone and oxycodone. However, a number of adverse side effects associated with the administration of tramadol, e.g., dizziness, somnolence, nausea, constipation, sweating and pruritus, are similar to that of the opioids. Since tramadol causes significantly less respiratory depression than the opioids, any enhancement, or potentiation, of the analgesic activity of tramadol would allow the dosage level of the drug to be reduced below that of the standard dosage level without a reduction in analgesic response. Alternatively, potentiation of tramadol would allow the standard dosage level to be maintained but with an increase in analgesic response. Either way, the safety of tramadol-induced analgesia will have been considerably improved by a potentiation of its analgesic effectiveness.
Dextromethorphan is the d-isomer of the codeine analog of levorphanol. Unlike the l-isomer, dextromethorphan is said to have no analgesic or addictive properties (Goodman and Gilman's, "The Pharmacological Basis of Therapeutics", 8th ed., McGraw-Hill, Inc. (1990), p. 518).
U.S. Pat. No. 5,336,691 describes an analgesic composition containing tramadol and acetaminophen alone, optionally in combination with an antitussive agent such as dextromethorphan, caraminophen and acceptable salts thereof.
Heretofore, there has been no recognition or appreciation that the analgesic effectiveness of tramadol can be appreciably enhanced by administration of tramadol prior to, with or following the administration of an analgesia-enhancing amount of dextromethorphan or for that matter, any other NMDA receptor antagonist.